Supreme delivery effect of β-cyclodextrin for hypoxic cancer cells recognized in 2019 Nobel prize laureate’s lab

Posted by

2019 Nobel prize in Physiology or Medicine will be awarded to William G. Kaelin Jr., Sir Peter J. Ratcliffe and Gregg L. Semenza for their discoveries of how cells sense and adapt to oxygen availability. Professor Semenza is currently the Director of the Vascular Research Program at the Johns Hopkins Institute for Cell Engineering in Baltimore, Maryland. This city has hosted high profile cyclodextrin research for decades, no wonder that CD technology did neither avoid Professor Semenza’s laboratory.

In one of projects run at his lab, pancreatic tumor was studied in vitro and in vivo. This tumor type is notable for being composed of several distinctive, cellular, and noncellular elements including a collagen-rich, poorly vascularized and highly hypoxic, non-neoplastic stroma. These characteristics are associated with chemoresistance to the most commonly used systemically applicable anticancer agents. The therapeutic efficacy of a <<systemically administrable>> formulation of 3-bromopyruvate was studied in the form of being encapsulated into a complex with β-cyclodextrin. (short note of the editor: probably the cyclodextrin community and regulatory authorities would be cautious about the systemic applicability of native β-cyclodextrin as used in a nanoencapsulated formulation and would rather recommend HPBCD derivative as alternative whose systemic application was actually elaborated in Baltimore in the 1980s mainly owing to the work of Josef Pitha at NIH).

In vivo, animals treated with β-cyclodextrin–3-bromopyruvate demonstrated minimal or no tumor progression as opposed to animals treated with gemcitabine or the β-cyclodextrin. In contrast to animals treated with free 3-bromopyruvate, no lethal toxicity was observed for β-CD–3-bromopyruvate.

By this blog entry we congratulate all the three novel Nobel laureates!

Reference:

Julius Chapiro, Surojit Sur, Lynn Jeanette Savic, Shanmugasundaram Ganapathy-Kanniappan, Juvenal Reyes, Rafael Duran, Sivarajan Chettiar Thiruganasambandam, Cassandra Rae Moats, MingDe Lin, Weibo Luo, Phuoc T. Tran, Joseph M. Herman, Gregg L. Semenza, Andrew J. Ewald, Bert Vogelstein and Jean-François Geschwind: Systemic Delivery of Microencapsulated 3-Bromopyruvate for the Therapy of Pancreatic Cancer Clin Cancer Res December 15 2014 (20) (24) 6406-6417; DOI: 10.1158/1078-0432.CCR-14-1271

IMAGE CREDIT: WILL KIRK / JOHNS HOPKINS UNIVERSITY

 

 

Leave a Reply

This site uses Akismet to reduce spam. Learn how your comment data is processed.